Chapter
1: SOME PRINCIPLES
1.
How is it possible to discover the functions of the 'non-coding' sequences
in and around a gene? To what extent have these techniques yielded satisfactory
answers?
2. Repetitive DNA sequences are a major component of mammalian genomes.
Describe the different classes of such sequences, and outline what -
if any - biological function they may serve.
3. Write an essay on the recognition of information in nucleic acids.
4.
What forces maintain the structure of a DNA duplex?
5.
Illustrate how differences between the structure of DNA and RNA are
reflected in the ways that proteins interact with them.
6.
Genes have been defined in many different ways over the years. Describe
as many of these ways as you can. What definition is appropriate today?
7.
What is DNA supercoiling? How is it generated? What are its biological
roles?
8.
Discuss redundancy in the genome, and the roles that it plays.
9.
Estimates for gene numbers suggest that mammals have four times more
genes than flies, and ten times more than yeast. Discuss.
10.
What is the role of the nuclear membrane?
11.
What are the three primary lineages of the living world, and how do
they differ?
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Chapter
2- STRUCTURE
1. How
is the structure of the nuclear pore related to its function?
2. Discuss
how proteins are imported into the nucleus.
3. Describe
what we know about the synthesis and processing of ribosomal RNA.
4. Would
you describe the nucleolus as a ribosome factory, when we know so little
about the assembly of ribosomal RNA into a ribosome?
5. Describe
the hierarchies of organization of DNA from the double helix to the
chromosome. What problems does the organization pose for transcription
and replication?
6.
How is the structure of DNA in the isolated 'nucleoid' related to that
found in vivo?
7. What
is the evidence that clusters of chromatin loops are organized into
'clouds' around transcription 'factories'?
8.The
cytoplasm contains a well-characterized skeleton. Discuss the evidence
for and against the existence of an analogous skeleton within the nucleus.
9. Write
an essay on compartmentalization in the nucleus.
10.Why
has it been so difficult to determine the structure of a eukaryotic
chromosome, whether in interphase or mitosis?
11.Most
eukaryotic chromosomes have similar shapes, even though they may contain
very different amounts of DNA. How adequately do current models for
the organization of the DNA fiber within a chromosome account for its
general shape?
12.Discuss
current models for the structure of chromatin and chromosomes. How far
do they account for the various functions of DNA?
13.What
are polytene chromosomes, and how are they formed?
14.Why
do mitotic chromosomes have the shape they do?
15.
Discuss telomeres in terms of their discovery, location, universality,
duplication, and relationship with ageing and cancer.
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Chapter
3 - REPLICATION
1. Discuss
the evidence for and against the idea that active DNA polymerases are
organized into factories.
2. What
problems does the double-helical structure of DNA pose for the process
of replication?
3. Describe
the roles of the different proteins involved in replicating a DNA duplex.
4.
How does the process of replication on one side of a replication fork
differ from that on the other?
5. DNA
polymerases make mistakes. Describe the mechanisms that ensure that
parental and daughter duplexes have the same DNA sequences.
6. Describe
how the origins of replication in pro- and eu-karyotes can be defined.
7. Compare
and contrast the origins of replication found in simple organisms with
those of mammalian cells.
8. 'There
is no such thing as a specific origin of DNA replication in eukaryotes'.
Discuss.
9.
Discuss the role played by transcription during replication.
10.
Discuss the problems associated with replicating the ends of a chromosome.
How are these problems solved?
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Chapter
4 - TRANSCRIPTION
1. Describe
the topological problems associated with transcribing a double-helical
template. How are these problems solved?
2. Outline
the molecular events that lead to the synthesis of a primary transcript
by RNA polymerase II, and describe how evidence for the process was
obtained.
3.
Discuss the evidence for and against the idea that active RNA polymerases
are organized into factories.
4. Describe
the properties of the three eukaryotic RNA polymerases and their templates.
5. Comparison
of the promoter sequences of a family of mammalian genes reveals that
all share a sequence of eight nucleotides. Outline how you would test
experimentally the possible role of this octamer sequence in regulating
the expression of these genes.
6. Outline
the modifications that occur to ribosomal RNA as it matures. How were
these modifications discovered?
7. The
initiation of transcription by eukaryotic RNA polymerases requires the
assembly of a large complex. Outline the order of events that result
in initiation, and indicate the type of molecular interactions that
are involved.
8. RNA
polymerases make mistakes. Describe the mechanisms that ensure that
messages contain the correct coding information.
9. To
what extent can a transcriptional activity found in vivo be reproduced
in vitro?
10.
Discuss the role played by the C-terminal domain of RNA polymerase II
in the production of a transcript.
11.
Describe how a transcript made by RNA polymerase II is modified.
12.
How are primary transcripts processed and what roles do such modifications
play?
13.
Describe the role played by RNA:RNA interactions in the removal of introns
from the primary transcript of eukaryotic genes transcribed by RNA polymerase
II.
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Chapter
5 - REPAIR
1. Describe
the lesions that are commonly found in DNA. What are the consequences
if they go unrepaired?
2. Discuss
the advantages and disadvantages of the different approaches that have
been used to detect the ways in which damaged templates are normally
repaired.
3. Illustrate
how the study of human disease has helped us to understand the different
pathways involved in repairing damage in DNA.
4. Compare
and contrast the major pathways involved in repairing damage in human
DNA.
5. What
are the consequences of a failure to repair damaged templates?
6.
Genomes seem to contain more genes involved in repairing DNA than in
replicating it. Why?
7. Outline
the evidence that some repair of damage in DNA is coupled to transcription.
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Chapter
6 - REGULATION OF GENE EXPRESSION
1.
The expression of bacterial genes is controlled by the action of diffusible
repressors and activators. To what extent is the expression of mammalian
genes controlled similarly?
2.
How true is the statement that all cells in a mammal contain the same
genetic information?
3.Outline
the various levels at which the expression of genes is controlled? What
methods would you use to identify which control mechanisms were operating
in a particular case?
4.
The differentiated state is generally stable and can be inherited from
one somatic cell to another. What mechanisms might account for this
stability and how might you distinguish experimentally between them?
5.
Describe the experimental approaches that have been used to analyze
how gene expression is regulated at the level of the nucleosome (and/or)
chromatin loop?
6.
How do covalent modifications of histones and DNA affect gene expression?
7.
How far has a detailed knowledge of the nucleotide sequence in and around
genes helped to explain their tissue-specific expression?
8.
Discuss the relative importance of cis- and trans-acting factors in
the control of transcription.
9.
Discuss the advantages and disadvantages of the various approaches being
used to obtain an understanding of tissue-specific gene expression?
10.
Are locus control regions any different from transcriptional enhancers?
11.
Describe the experimental approaches used to define enhancers and locus
control regions, and explain how the functions of the two sequences
differ.
12.
What are the major factors underlying the inactivity of heterochromatin?
13.
'Methylation of DNA results from, but does not cause, differentiation.'
Discuss.
14.
How close are we to a complete molecular definition of the inactivity
of heterochromatin?
15.
Outline the various mechanisms that are involved in creating (and/or
maintaining) the differentiated state.
16.
'The techniques of structural biology have told us little about the
regulation of gene expression that we did not already know'. Discuss.
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Chapter
7 - THE CELL CYCLE
1.
Discuss the role that microtubules play in chromosome segregation.
2.
The spindle contains millions of moving parts. How are these movements
controlled?
3.
Centromeres exhibit a bewildering structural variation. What are their
main functions?
4.
The cell cycle is regulated by the reversible phosphorylation of proteins.
Discuss.
5.
How is the synthesis of DNA controlled in eukaryotes?
6.
Review the evidence supporting current models for the initiation of
DNA replication in eukaryotic cells.
7.
Compare the checkpoints in the cell cycles of yeast and man.
8.
Assess the evidence that the mechanisms for controlling passage through
the cell cycle are conserved in eukaryotes.
9.
Review the mechanisms that ensure orderly progression through the cell
cycle.
10.
Discuss the evidence that genetic defects are responsible for malignancy.
11.
Describe the advantages and disadvantages of the various approaches
being used to identify genes involved in cancer.
12.
Discuss the view that malignancy results from an imbalance in the activity
of oncogenes and anti-oncogenes.
13.
Cancer is a multi-step process. Discuss.
14.
How have studies of the nematode, Caenorhabditis elegans, contributed
to our understanding of apoptosis? How does the process in the worm
differ from that in higher vertebrates?
15.
How is the apoptotic machinery controlled?
16.
'Cancer chemotherapy owes nothing to molecular biology.' Discuss.
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Chapter
8 - MEIOSIS AND RECOMBINATION
1.
Compare and contrast the processes of mitosis and meiosis.
2.
Discuss the roles that the synaptonemal complex and the chiasma play
during meiosis.
3.
Describe the mechanisms involved in the exchange of genetic information
from one chromosome to another.
4.
Describe the phenomenon of gene conversion in yeast.
5.
How effectively do current models account for the properties of meiotic
and mitotic recombination?
6.
The breaking and joining of DNA are widespread in both prokaryotes and
eukaryotes. What do we know of the various mechanisms that are used
in these processes?
7.
How do chromosomes pair?
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